Inflammation in the Genesis and Perpetuation of Cancer: Summary and Recommendations from a National Cancer Institute–Sponsored Meeting

Abstract

The Inflammation and Cancer Think Tank Meeting was organized by the National Cancer Institute with the purpose of identifying research advances, gaps, and opportunities for the study and clinical application of the role of inflammation on tumorigenesis. The format of this meeting consisted of brief presentations that focused on concepts, with extensive discussion periods to allow participants to identify issues and barriers limiting progress in this area. The strong relationship between inflammation and cancer in the gastrointestinal tract prompted several presentations that were focused on carcinogenesis within this organ system; however, many of the same immune mediators that influence esophageal, gastric, and colorectal carcinoma were also shown to influence inflammation-related malignancies at other anatomic sites. This article summarizes the findings of this Think Tank Meeting, which highlight the intimate relationship between malignant cells and their inflammatory microenvironment and specifically address opportunities to manipulate the host immune response and therefore intervene at different points along the tumorigenic cascade. (Cancer Res 2005; 65(19): 8583-7)

Endothelial Akt Signaling Is Rate-Limiting for Rapamycin Inhibition of Mouse Mammary Tumor Progression

“…Using the mouse spontaneous mammary tumor model MMTV-PyT, we tested the ability of rapamycin to inhibit tumor growth at these doses. We initiated rapamycin treatment when the tumors first became palpable, at which point they had passed the angiogenic switch and were 50 to 100 mm 3 . We observed effective inhibition of tumor growth in control DTG mice at 0.1 and 0.5 mg/kg/d (Fig.…”

“…The importance of the tumor microenvironment in regulating tumor growth and progression has been recently appreciated and targeted for therapy (1)(2)(3). Although there is evidence that the tumor stroma can acquire mutations and epigenetic alterations (4,5), it is still believed that most cells which are resident in the tumor microenvironment are more genetically stable than tumor cells and retain more normal responses to growth signals and other metabolic cues.…”

Chronic inflammation that facilitates tumor progression creates local immune suppression by inducing indoleamine 2,3 dioxygenase

“…There is growing recognition that inflammatory processes nurture developing malignancies in tissues before overt tumors are established (36). Local inflammation triggers the release of factors that can support the outgrowth of premalignant cells (37), whereas inflammation-associated immune activation may eliminate tumors or promote malignant progression by positively selecting for immune escape variants, a process collectively referred to as ''immunoediting'' (38).…”

Targeting Molecular Pathways for Prevention of High Risk Breast Cancer: A Model for Cancer Prevention

“…For example Helibacter pylori infection and gastric cancer, inflammatory bowel disease and colon cancer, and hepatitis and hepatocellular carcinoma [28][29][30]. Subsequent studies that revealed an inverse relationship between long-term usage of anti-inflammatory medications and a decreased cancer risk support the support the direct association between chronic inflammation and cancer development [31]. Through a variety of cellular mediators, chemokines and cytokines, innate immune cells and T H 2 cells are able to create a pro-tumor microenvironment that favors cell proliferation, genomic instability and malignant conversion [32].…”